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Renal Dysfunction and Tubulopathy Induced by High-Dose Tenofovir Disoproxil Fumarate in C57BL/6 Mice.
Jang, Eungyeong; Lee, Jong Kil; Inn, Kyung-Soo; Chung, Eun Kyoung; Lee, Kyung-Tae; Lee, Jang-Hoon.
Afiliación
  • Jang E; Department of Internal Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea.
  • Lee JK; Department of Internal Medicine, Kyung Hee University Korean Medicine Hospital, Seoul 02447, Korea.
  • Inn KS; Department of Fundamental Pharmaceutical Science, Graduate School, Kyung Hee University, Seoul 02447, Korea.
  • Chung EK; Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Korea.
  • Lee KT; Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea.
  • Lee JH; Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Korea.
Healthcare (Basel) ; 8(4)2020 Oct 21.
Article en En | MEDLINE | ID: mdl-33096887
Tenofovir disoproxil fumarate (TDF) is the most preferred antiretroviral medicine in treating human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infections. Recent clinical trials have reported conflicting results on renal toxicity and safety in TDF-treated patients, but reference animal studies, testing high-doses of TDF for renal toxicity, are scarce. In this preclinical study, we investigated whether daily oral TDF administration (200, 500, or 800 mg/kg/d, p.o.) for four weeks induces renal insufficiency in C57BL/6 mice, by evaluating changes in body weight, urine micro-total protein, urinary microalbumin, serum blood urea nitrogen (BUN), and creatinine levels, along with histological examination of kidney samples. In the G3 group (TDF 800 mg/kg/d, p.o.), three mice died on the 17th, 23rd and 26th days, and overall, significant increases in urinary and serum levels were observed after two weeks of TDF treatment. In addition, the proportion of pyknotic epithelial cells and acidophilic cytoplasm in renal tubules was also increased after two weeks, and congestion and hemorrhage were observed in renal tubules after three weeks. Taken together, high-dose TDF treatment of 800 mg/kg/d might lead to renal tubular damage and dysfunction, great enough to cause death in mice, even after a short period of one to two weeks.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Healthcare (Basel) Año: 2020 Tipo del documento: Article Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Healthcare (Basel) Año: 2020 Tipo del documento: Article Pais de publicación: Suiza